Corticosterone mediates electroacupuncture-produced anti-edema in a rat model of inflammation

Abstract

Background: Electroacupuncture (EA) has been reported to produce anti-edema and anti-hyperalgesia effects on inflammatory disease. However, the mechanisms are not clear. The present study investigated the biochemical mechanisms of EA anti-inflammation in a rat model.

Methods: Three experiments were conducted on male Sprague-Dawley rats (n = 7-8/per group). Inflammation was induced by injecting complete Freund's adjuvant (CFA) subcutaneously into the plantar surface of one hind paw. Experiment 1 measured plasma corticosterone (CORT) levels to see if EA regulates CORT secretion. Experiment 2 studied the effects of the adrenal gland on the therapeutic actions of EA using adrenalectomy (ADX) rats. Experiment 3 determined whether a prototypical glucocorticoid receptor antagonist, RU486, affects EA anti-edema. EA treatment, 10 Hz at 3 mA and 0.1 ms pulse width, was given twice, for 20 min each, once immediately after CFA administration and again 2 h post-CFA. Plasma CORT levels, paw thickness, indicative of the intensity of inflammation, and paw withdrawal latency (PWL) were measured 2 h and 5 h after the CFA injection.

Results: EA significantly increased plasma corticosterone levels 2 h (5 folds) and 5 h (10 folds) after CFA administration compared to sham EA control, but EA alone in naive rats and CFA alone did not induce significant increases in corticosterone. Adrenalectomy blocked EA-produced anti-edema, but not EA anti-hyperalgesia. RU486 (15 mul, 15 mug/mul), a prototypical glucocorticoid receptor antagonist, also prevented EA anti-edema.

Conclusion: The data demonstrate that EA activates the adrenals to increase plasma corticosterone levels and suppress edema and suggest that EA effects differ in healthy subjects and in those with pathologies.

Figure 1

Effects of EA treatment on plasma levels of CORT. The data were presented as % changes vs baseline (n = 8 per group, mean ± SEM). EA treatment in non-inflamed rats (diamond) induced no significant changes of plasma CORT. CFA-induced inflammation alone (triangle) resulted in no significant changes in plasma CORT levels. EA treatment in inflamed rats (circle) significantly increased CORT levels compared to sham EA (square). *P < 0.05 compared sham EA.

Figure 2

EA effects on edema in ADX rats. The data were presented as mean ± SEM. All rats (n = 7 per group) were CFA-inflamed. Note that EA did not inhibit edema in ADX rats. Edema was determined by increased paw thickness (mm).

Figure 3

Effects of RU486 on EA anti-edema in CFA-inflamed rats. The data were presented as mean ± SEM. The hind paw thickness is the average of values at 2 h and 5 h and was analyzed with two-way ANOVA (n = 7 per group). EA + vehicle (column 1) significantly alleviated edema compared to sham + vehicle control (column 2). After RU486 pretreatment (columns 3 & 4), EA showed no anti-edema effects (column 3) compared to sham control (column 4). * p < 0.05 compared to sham EA.

Figure 4

EA effects on hyperalgesia in ADX rats. The data were presented as mean ± SEM. All rats (n = 7 per group) were inflamed with CFA. Note that EA significantly inhibited hyperalgesia at 2.5 h post-CFA in ADX rats. Hyperalgesia was defined as a decrease in PWL (sec). * p < 0.05 compared to sham EA.